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Biomedical subjects

M Noguchi

Publications and source records attributed to M Noguchi.

At least 127 records · Page 7Linked to original sources
PubMed1999

Activation of matrix metalloproteinase-2 in human breast cancer cells overexpressing cyclooxygenase-1 or -2.

Human breast cancer cell line Hs578T was stably transfected with cDNA for cyclooxygenase-1 or -2. When the cells overexpressing cyclooxygenase-1 or -2 were stimulated with concanavalin A, the processing of matrix metalloproteinase-2 was observed with the aid of gelatin zymography. This processing was not seen in mock-transfected and original cells which did not express detectable cyclooxygenase activity. Furthermore, Northern blotting showed 8-13 fold induction of membrane-type 1 matrix metalloproteinase which processed matrix metalloproteinase-2 in the cells expressing cyclooxygenases. These findings suggest that both isoforms of cyclooxygenase mediate the processing of matrix metalloproteinase-2 through induction of membrane-type I metalloproteinase in breast cancer cells.

Breast Neoplasms↗
PubMed1999

Ferric alpha-hydroxyheme bound to heme oxygenase can be converted to verdoheme by dioxygen in the absence of added reducing equivalents.

Whether or not reducing equivalents are indispensable for the conversion of ferric alpha-hydroxyheme bound to heme oxygenase-1 to verdoheme remains controversial (Matera, K. M., Takahashi, S., Fujii, H., Zhou, H., Ishikawa, K., Yoshimura, T., Rousseau, D. L., Yoshida, T., and Ikeda-Saito, M. (1996) J. Biol. Chem. 271, 6618-6624; Liu, Y., Moënne-Loccoz, P., Loehr, T. M., and Ortiz de Montellano, P. R. (1997) J. Biol. Chem. 272, 6906-6917). To resolve this controversy, we have prepared a ferric alpha-hydroxyheme-heme oxygenase-1 complex and titrated the complex with O2 under strictly anaerobic conditions. The formation of verdoheme was monitored by optical and electron spin resonance spectroscopies. Electron spin resonance spectra of the complex showed that alpha-hydroxyheme exists as a mixture of resonance structures composed of the iron(III) porphyrin and the iron(II) porphyrin pi neutral radical. Upon addition of CO the latter species becomes dominant. The results obtained from these titration experiments indicate that alpha-hydroxyheme can be converted to verdoheme by an approximately equimolar amount of O2 without any requirement for exogenous electrons. The verdoheme formed from alpha-hydroxyheme was shown to be in the ferrous oxidation state by the addition of CO or potassium ferricyanide to the resultant verdoheme-heme oxygenase-1 complex.

Electron Spin Resonance Spectroscopy↗
PubMed1999

Correlation between the status of the p53 gene and survival in patients with stage I non-small cell lung carcinoma.

The association of p53 abnormalities with the prognosis of patients with non-small cell lung carcinoma (NSCLC) has been extensively investigated to date, however, this association is still controversial. Therefore, we investigated the prognostic significance of p53 mutations through exons 2 to 11 and p53 protein expression in 103 cases of stage I NSCLC. p53 mutations were detected in 49 of 103 (48%) tumors. Two separate mutations were detected in four tumors giving a total of 53 unique mutations in 49 tumors. Ten (19%) of mutations occurred outside exons 5-8. Positive immunohistochemical staining of p53 protein was detected in 41 of 103 (40%) tumors. The concordance rate between mutations and protein overexpression was only 69%. p53 mutations, but not expression, were significantly associated with a shortened survival of patients (P<0.001). Furthermore, we investigated the correlation between the types of p53 mutations and prognosis. p53 missense mutations rather than null mutations were associated with poor prognosis (P < 0.001 in missense mutations and P=0.243 in null mutations). These results indicated that p53 mutations, in particular missense mutations, rather than p53 expression could be a useful molecular marker for the prognosis of patients with surgically resected stage I NSCLC.

Alleles↗
PubMed1999

Prospective Randomized Study of Cyclophosphamide, Epirubicin, and 5-Fluorouracil versus Cyclophosphamide, Adriamycin, and 5-Fluorouracil in Advanced or Recurrent Breast Cancer.

BACKGROUND: Treatment with cyclophosphamide, adriamycin, and 5-fluorouracil (CAF), a widely used, potent regimen is sometimes restricted by the myelotoxicityand myocardiotoxicity of adriamycin (ADR). In a prospective randomized controlled study of patients with advanced or recurrent breast cancer, the efficacy and toxicity of a CEF regimen, in which epirubicin (EPI) was substituted for ADR, was compared with CAF. METHODS: 138 female patients under 75 years of age who had unresectable or recurrent breast cancer during the period from October, 1989 to September, 1991, were randomized to one of two treatment regimens. The first regimen consisted of cyclophosphamide 100 mg p.o. d1-14, adriamycin 30 mg/m(2) i.v. d1, 8 and 5-fluorouracil 500 mg/m(2) i.v. d1, 8 (CAF). In the second regimen, EPI 30 mg/m(2) i.v. d1, 8was substituted for ADR (CEF). Both regimens were delivered q4 weeks. RESULTS: Of 138 patients, 105 (CEF 56, CAF 49) were evaluable for response and survival, and all were evaluable for toxicity (CEF 68, CAF 70). The median course of lots CEF and CAF was 3 cycles. Response rates (complete response plus partial response) with CEF and CAF were 35.7% (20/56) and 36.7% (18/49), respectively. Adverse effects were similar in the two groups, but severe leukopenia (CEF 36.8%, CAF 64.3%) and hepatic toxicity (CEF 1.5%, CAF 12.9%) were encountered more frequently with CAF than with CEF. The duration of 50% survival was 135.9 weeks for CEF and 172.1 weeks for CAF (not significant). CONCLUSION: At an equal dose of EPI and ADR response rates and survival of the CEF group were similar to those of the CAF group, but adverse effects were fewer in the CEF group.

Journal Article↗
PubMed1999

The Outcome of Patients with Breast Cancer Who Underwent Breast Conserving Treatment with or without Immediate Volume Replacement with Autogenous Tissue.

BACKGROUND: Breast conserving treatment (BCT) is accepted as an appropriate therapy for most patients with stage I and stage II breast cancer. However, BCT is associated with a relatively high incidence of local recurrence, and aesthetically unacceptable results occur in some patients. A novel method of immediate volume replacement using autogenous tissue has been developed to strike a balance between adequate excision and cosmesis. We determined the oncological outcome inpatients with breast cancer treated with wide excision, immediate volume replacement with autogenous tissue, and axillary dissection followed by radiotherapy. METHODS: One hundred fifty-three patients with TIS, stage I, II, or III breast cancer underwent wide excision and axillary dissection. The surgical margin ofexcised breast tissue was examined histologically during surgery. If involved, the breast tissue adjacent to the primary site was excised. When the margin of re-excision was positive, patients underwent modified radical mastectomy with or without breast reconstruction. After wide excision, immediate volume replacementwith autogenous tissue was perform-ed, unless the deformity was corrected by undermining and conization of the residual breast tissue. Postoperatively, all patients received breast irradiation. RESULTS: Eighteen patients underwent modified radical mastectomy. The surgical margin was negative in 132 of the 135 patients who underwent BCT. The crude local recurrence rate was 0.7% (1/135). Estimated overall and disease-free 5-year survival rates were 96% and 94%, respectively. CONCLUSION: Wide excision with tumor-free margins and axillary dissection followed by breast irradiation provides adequate local control in many patients with breast cancer. Immediate breast volume replacement with autogenous tissue mayavoid some unpleasant cosmetic results associated with extensive local resection. Our technique eliminates the need for mastectomy in selected patients.

Journal Article↗
PubMed1999

Binding characteristics of dialkyl phthalates for the estrogen receptor.

Dialkyl phthalates have been suggested to function as xenoestrogen. To explore the structural essentials, a series of ring and alkyl-chain isomers of dialkyl phthalates C6H4(COOCnHm)2 were examined for their ability to displace [3H]17beta-estradiol in the recombinant human estrogen receptor expressed on Sf9 vaculovirus. Compounds with an alkyl chain of more than C3 (n = 3) exhibited a distinct full receptor binding in a dose-dependent manner. When the ring isomers of C3-diallyl (-CH2-CH=CH2) derivatives, namely diallyl phthalate, diallyl isophthalate, and diallyl terephthalate, were examined, the ortho isomer of diallyl phthalate was most potent to bind to the estrogen receptor. The interaction with the estrogen receptor was optimized with dibutyl phthalates of C4. The conformational studies by 1H-NMR measurements and ab initio molecular orbital calculations have suggested that the structure mimics the interface of steroid A and B/C rings of 17beta-estradiol. Dicyclohexyl phthalate bound to the estrogen receptor with a biphasic binding curve, suggesting the compound discriminates two different receptor conformations.

Binding, Competitive↗
PubMed1999

Enhanced production and activation of progelatinase A mediated by membrane-type 1 matrix metalloproteinase in human papillary thyroid carcinomas.

Matrix metalloproteinases (MMPs) are believed to be involved in the invasion and metastasis of various human carcinomas. In the present study, the production levels of seven different MMPs (MMP-1, -2, -3, -7, -8, -9, and -13), the activation of the zymogen of MMP-2 (proMMP-2), the expression of membrane-type MMPs (MT1-, MT2-, and MT3-MMPs), and the tissue localization of the activated enzyme were examined in human invasive papillary thyroid carcinomas. Sandwich enzyme immunoassays revealed that among the MMPs examined, only the MMP-2 production level is significantly enhanced in the carcinoma tissues compared with the follicular adenoma and normal control thyroid tissues. Gelatin zymography indicated that the proMMP-2 activation ratio is considerably higher in carcinomas with lymph node metastasis than it is in those without metastasis, follicular adenomas, or normal controls (P < 0.01). Northern blot analysis of the expression of MT1-, MT2-, and MT3-MMPs, which are known to activate proMMP-2 in vitro, demonstrated the predominant expression of MT1-MMP mRNA in the carcinoma tissues (15 of 15 cases), whereas MT2-MMP expression was confined to 26% of the cases (4 of 15 cases), and no consistent expression of MT3-MMP was observed. MTI-MMP mRNA expression levels correlated with the proMMP-2 activation ratio (r = 0.692; P < 0.01), but such a correlation was not obtained with MT2-MMP. There was also a direct correlation between MT1-MMP expression and lymph node metastasis (P < 0.05). In situ hybridization indicated that both carcinoma and stromal cells express MT1-MMP transcripts (five of six cases). MT1-MMP was also immunolocalized to carcinoma and stromal cells in all of the carcinoma samples (26 of 26 cases), which were positive for MMP-2. In situ zymography indicated definite gelatinolytic activity in the carcinoma cell nests, which was abolished by incubation of the carcinoma samples with a synthetic MMP inhibitor before the reaction. These results suggest for the first time that among seven different MMPs, the production of proMMP-2 and its MT1-MMP-mediated activation in the carcinoma cell nests play an important role in the lymph node metastasis of human invasive papillary thyroid carcinomas.

Adult↗
PubMed1999

Monitoring and antibacterial treatment for postoperative bacterial overgrowth in Crohn's disease.

PURPOSE: Bacterial overgrowth sometimes complicates the clinical course of Crohn's disease and may lead to inappropriate treatment. To clarify the effect of antibiotic therapy, we monitored the hydrogen concentration in expiratory breath after fasting. METHODS: We evaluated 18 patients (15 males; median age, 32.7; range, 22.3-60 years) for postoperative bacterial overgrowth symptoms and for intestinal dilation by plain abdominal x-ray. Five patients had ileitis and 13 patients had ileocolitis. Various intestinal resections were performed in all, and strictureplasties were done at the same time in 13 patients. The median postoperative period was 10.2 (range, 1.2-102) months. Nine patients, who had symptoms such as bloating, nausea, vomiting, or pain, were classified as the symptomatic group, whereas nine other patients, who had no symptoms, were classified as the symptom-free group. Sixteen patients who had undergone intestinal resections for noninflammatory bowel disease served as the control group. After overnight fasting, hydrogen concentration in end-expiration, breath was measured with gas chromatography. At the same time clinical examinations of white blood cell count, hemoglobin, total protein, serum albumin, iron, sialic acid, and C-reactive protein in the peripheral blood were performed. To assess the effect of antibacterial treatment, changes in symptoms were assessed in eight patients who received antibacterial treatment. Hydrogen concentration was measured repeatedly before and after treatment in six patients. RESULTS: The symptomatic group had an expiratory hydrogen concentration level significantly higher (median, 40; range, 20-139 ppm) than the control group (median, 3; range, 1-6 ppm) and the symptom-free group (median, 4; range, 1-10 ppm). After the antibiotic treatment the symptoms were improved in all of the patients, and the hydrogen concentration level was significantly reduced (median, 4.5; range, 2-13 ppm). CONCLUSIONS: Antibacterial treatment was useful in the postoperative patients whose assessments were complicated by bacterial overgrowth. Using a hydrogen breath test, bacterial overgrowth was effectively monitored and managed, effecting a change in clinical symptoms.

Adult↗
PubMed1999

Spontaneously developed aneurysm of the ductus arteriosus in an adult.

We report an unusual adult case of aneurysm associated with the ductus arteriosus. A 67-year-old female, who suffered recurrent nerve palsy, was diagnosed as having an aneurysm of the ductus arteriosus. The aneurysm, located in the medial aspect of the aortic ischimus and projected toward the pulmonary artery, was successfully repaired using a Dacron patch. A pathologic review of the aneurysm revealed the degeneration of the aortic media.

Aged↗
PubMed1999

Anomalous systemic arterial supply to normal basal segments of the left lower lobe.

BACKGROUND: Anomalous arterial supply to the normal basal segments of the lower lobe without sequestration is a rare congenital abnormality, and whether it belongs to the broad spectrum of sequestration disorders remains controversial. METHODS: The cases of all 4 patients who were treated surgically by us were reviewed together with 8 previously reported cases. RESULTS: The anomalous artery originated from the descending thoracic aorta, distributed to the basal segments of the left lower lobe, and drained to a normal inferior pulmonary vein in each case. The anomalous artery was thick and elastic walled. From the review of all 12 cases, male gender, left side, descending thoracic aorta as the aberrant arterial origin, absence of pulmonary blood flow to the basal segments, and normal pulmonary venous drainage were predominant. Despite some differences, the findings seemed closely related to intralobar sequestration. Surgical treatments were lung resection, anastomosis, and ligation of the anomalous artery. CONCLUSIONS: This anomaly is probably one type of sequestration complex. Both aortic and pulmonary arterial angiographic studies are needed to plan the definitive surgical procedure.

Adult↗
PubMed1999

Biochemical markers of bone turnover during hormone replacement therapy.

OBJECTIVE: To assess the clinical usefulness of bone turnover markers, including serum osteocalcin (OC), urinary pyridinoline (Pyr) and deoxypyridinoline (D-Pyr), in monitoring and predicting bone response to hormone replacement therapy (HRT). METHOD: The relationships between baseline levels or changes in markers and change in lumbar bone mineral density were examined in 21 surgically-induced postmenopausal women. RESULTS: Levels of OC, Pyr and D-Pyr in the estrogen effective group (responders) significantly decreased during HRT and baseline levels of Pyr and D-Pyr in responders were significantly higher than those in premenopausal women. CONCLUSION: Bone turnover markers were useful in monitoring the bone effect of HRT and baseline levels of markers reflect subsequent bone response to HRT.

Amino Acids↗
PubMed1999

Disruption of gap junctional intercellular communication in human renal cancer cell lines.

OBJECTIVES: Gap junctional intercellular communication (GJIC) is believed to play an important role in the maintenance of cell homeostasis, and its disruption may be associated with carcinogenesis. However, GJIC has not been detected in many human cancers. We therefore studied the regulation of GJIC in human renal cancer cell lines. METHODS: We examined the human renal cancer cell lines, ACHN and NT, as well as Madin-Darby canine kidney (MDCK) cells as a positive control, using GJIC assays, Northern blotting to detect connexin 43 mRNA, immunofluorescent staining, and Western blotting of connexin 43 protein. RESULTS: GJIC of ACHN and NT was completely blocked. In ACHN cells, connexin 43 mRNA was not altered. However, connexin 43 protein was aberrantly localized and phosphorylated connexin 43 protein had disappeared. Both connexin 43 protein and its mRNA were undetectable in NT cells. CONCLUSIONS: GJIC in human renal cancer cell lines is impaired and various pathways may inhibit this mechanism in renal cancer. We believe that connexin plays an important role in renal carcinogenesis.

Carcinoma, Renal Cell↗
PubMed1999

All-trans retinoic acid enhances gap junctional intercellular communication among renal epithelial cells in vitro treated with renal carcinogens.

Epidemiological and clinical studies imply that retinoids have a chemopreventative action against cancer and can suppress the growth of cancer cells. The regulation of connexin (Cx) expression by retinoids varies among tissues and organs. In this study, we investigated whether all-trans retinoic acid (ATRA) upregulates gap junctional intercellular communication (GJIC) in renal epithelial cells exposed to renal carcinogens. Madin Darby canine kidney (MDCK) cells were incubated with ATRA for 3 days, then briefly exposed to 12-O-tetradecanoyl-phorbol-13-acetate (TPA) or renal carcinogens potassium bromate (KBrO3) and dimethylnitrosamine (DMN). ATRA increased the expression of connexin 43 mRNA and protein without affecting Cx 43 phosphorylation and prevented inadequate Cx 43 localisation caused by TPA/KBrO3 or DMN. Consequently, ATRA prevented the disruption of GJIC in MDCK cells. These data suggest that ATRA enhanced GJIC by upregulating Cx 43 expression and that ATRA might be useful for prevention of renal cell carcinoma.

Blotting, Western↗
PubMed1999

Sentinel lymphadenectomy in breast cancer: identification of sentinel lymph node and detection of metastases.

Sentinel lymphadenectomy is a useful way of assessing axillary status and obviating axillary dissection in patients with node-negative breast cancer. However, controversies remain concerning the optimal method to identify the sentinel lymph node (SLN) and detect micrometastases in this lymph node. We reviewed the literature concerning sentinel lymphadenectomy in breast cancer and reached the following conclusions: (a) A combination of preoperative lymphoscintigraphy with intraoperative dye-guided and gamma probe-guided methods achieves a higher rate of identification of SLN than any of these techniques alone. (b) Immediate and reliable intraoperative assessment of sentinel node status is vital to the technique's success. However, the reliability of sentinel node diagnosis using frozen sections is questionable, because micrometastatic foci cannot always be identified. (c) Hematoxylin and eosin (H&E) staining and/or immunohistochemistry on permanent sections are useful for the detection of micrometastases in the sentinel node. Although a reverse transcriptase-polymerase chain reaction (RT-PCR) method is more sensitive than H&E staining and immunohistochemistry, it would not distinguish benign from malignant epithelial cells in the SLN. Therefore, further study is required before sentinel lymphadenectomy gains general acceptance for patients with primary breast cancer.

Axilla↗